POS1436 CLINICAL CHARACTERISTICS AND RISK FACTORS OF INVASIVE FUNGAL INFECTION DURING IMMUNOSUPPRESSIVE INDUCTION THERAPY IN PATIENTS WITH CONNECTIVE TISSUE DISEASE
Authors: H. Fukui, H. Hanaoka, Y. Kaneko
Journal: Annals of the Rheumatic Diseases (2022)

Background Invasive fungal infection (IFI) is a life-threatening complication among immunosuppressed patients. Whereas intensive immunosuppressive therapy during remission induction phase in patients with connective tissue disease is a major risk of IFI, little is known about the clinical characteristics and risk factors of IFI. Objectives This study aims to reveal prevalence, clinical characteristics, and associated risk factors of IFI during immunosuppressive induction therapy in patients with connective tissue disease. Methods We reviewed consecutive patients with connective tissue diseases who underwent immunosuppressive remission induction therapy in Keio University Hospital Rheumatology Department from January 2012 to August 2020. Patients with 0.5mg/kg or more equivalent dose of daily prednisone use were included for IFI, diagnosed according to the definition of invasive fungal diseases from EORTC/MSG 2008. Infections caused by Pneumocystis jirovecii were not included. Results Among 2701 hospitalized cases, 627 patients had undergone induction or re-induction therapy. Total of 24(3.8%) patients were diagnosed as IFI, of whom there were 8 proven cases and 16 probable cases; 14 aspergillosis, 5 candidiasis, 2 cryptococcosis, 1 phaeohyphomycosis, and 2 cases with unknown pathogen. Median duration from the start of immunosuppressive therapy to the onset of IFI was 95 days (interquartile range, 36,249 days; range, 13-1397 days) and the mean dose of daily prednisolone was 0.53±0.29 mg/kg at the onset of IFI. Total of 11 patients died; 6 patients (25.0%) due to IFI and 5 patients (20.8%) due to the exacerbation of underlying disease. Univariable analysis comparing the IFI and non-IFI groups, age (65.8±3.7 vs. 56.1±0.7; P=0.01), initial prednisolone dose (0.87±0.01 vs 0.95±0.04 mg/kg; P=0.037), the history of methylprednisolone (mPSL) pulse therapy (54.2% vs. 20.0%; P&lt;0.001), tumor necrosis factor (TNF) inhibitor use (8.3% vs. 1.1%; P=0.039), 2 or more immunosuppressant or biologic use (33.3% vs. 12.9%; P=0.010), HbA1c 6.5% or higher (58.3% vs. 28.9%; P=0.003), lowest serum IgG during the clinical course (599.4±62.1 vs 787.7±12.4 mg/dl; P=0.003), and cytomegalovirus reactivation defined by pp65 antigen 6 or higher (33.3% vs. 11.2%; P=0.004) were significantly different, respectively. Sex, body mass index, presence of interstitial lung disease, and the use of cyclophosphamide, rituximab, or interleukin-6 inhibitors were not significantly different. Multivariable analysis revealed older age (for each 10-year increase: OR 1.40, 95% CI 1.03-1.91; P=0.023), the history of methylprednisolone pulse therapy (OR 2.60, 95% CI 1.06-6.77; P=0.049), TNF inhibitor use (OR 11.2, 95% CI 1.70-74.0; P=0.012), and serum IgG less than 550 mg/dl (OR 2.59, 95% CI 1.03-6.55; P=0.041) as the independent risk factors of IFI. Conclusion Patients with connective tissue disease with older age, lower serum IgG, mPSL pulse therapy, or TNF inhibitor use are at higher risk of IFI. Further studies are needed to determine the benefit of prophylactic anti-fungal treatment in such patients. References [1]De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis . 2008;46(12):1813-1821. Disclosure of Interests: None declared